Spurs are back at Europe’s top table and begin their campaign against the LaLiga side in north London, looking to build on their comfortable win over West Ham on Saturday.
Thomas Frank will be forced into at least one change from that match. Mathys Tel started up front at the London Stadium but he has been left out of Spurs’ squad for the league phase of this competition.
Richarlison is therefore expected to come back into the starting lineup, though Frank also has the option of giving Kolo Muani his first minutes in a Spurs shirt.
The Frenchman was an unused substitute against West Ham, with Frank previously speaking of the need to build his fitness, but he could feature against Villarreal.
“How many minutes? They can always play more minutes than we think. If we needed him to play he could play 90 minutes, but can he play at the intensity and the level we want? He is ready and he is involved tomorrow and that is the most important thing."
Dominic Solanke remains out with the ankle injury that saw him miss most of pre-season and then ruled him out of recent matches against Bournemouth and West Ham.
Frank has decisions to make across the pitch. Destiny Udogie will hope to come in for his first start of the season at full-back, while Rodrigo Bentancur could also return after dropping out against West Ham.
Xavi Simons started on the left wing in that match and has some promising moments without really catching the eye. Frank could be tempted to shift him into the No10 role, but that would likely mean at least one of Lucas Bergvall or Pape Matar Sarr miss out and both have been in impressive form.